CST6-mRNA activated matrices for efficient bone regeneration

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Project Summary Bone regeneration is a carefully orchestrated dynamic process that involves several key biological players, including growth factors and cells. Bone tissue engineering aims to provide an environment that facilitates and augments the natural bone regeneration process. CST6 is a cysteine protease inhibitor that is highly expressed in multiple myeloma patient samples lacking any bone lytic lesion, compared to those samples with at least one bone lytic lesion. In vitro pilot studies show that CST6 (in the recombinant protein form) promotes osteoblast differentiation and inhibit osteoclast differentiation. CmRNA has the unique advantage of functioning entirely in the cytoplasm (avoiding the need for nuclear entry) thereby, leading to a targeted transient expression of desired proteins with immense potential to overcome the challenges that exist with protein and DNA based approaches. Specifically, this study aims to develop a biomaterial-based delivery system that releases cmRNA (CST6) to induce in vivo bone regeneration. Our aims are 1) to demonstrate that nanoparticle loaded cmRNA (CST6) can efficiently trigger osteogenic differentiation and inhibit osteoclast maturation and 2) to assess bone regeneration efficacy of a collagen scaffold that delivers cmRNA (CST6) in unilateral diaphyseal femoral defects in rats